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AHA: Healthy Lifestyle Eases Heart Impact of High Genetic Risk

— Fewer adverse events, less calcification in pooled data

MedpageToday

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NEW ORLEANS -- Genes by themselves do not destine patients to coronary artery disease (CAD), a study reported, showing that a high genetic risk may be controlled with healthy lifestyle choices.

Patients at the top quintile of polygenic scores (indicating the highest genetic risk) had double the events as did their peers at the bottom quintile (HR 1.91, 95% CI 1.75-2.09), according to the BioImage study.

But a healthy lifestyle -- no current smoking, no obesity, regular physical activity, and a healthy diet or at least three of those criteria -- appeared to half the risk of coronary events for those high genetic-risk people compared with meeting only one or none of the healthy criteria (HR 0.54, 95% CI 0.47-0.63).

, of Massachusetts General Hospital in Boston, reported the BioImage study here at the annual American Heart Association meeting and simultaneously online in .

"Patients may equate DNA-based risk estimates with determinism, a perceived lack of control over the ability to improve outcomes," they concluded. "However, our results provide evidence that lifestyle factors may powerfully modify risk regardless of the patient's genetic risk profile."

"Although the absolute risk reduction that was associated with adherence to a healthy lifestyle was greatest in the group at high genetic risk, our results support public health efforts that emphasize a healthy lifestyle for everyone," the study authors wrote.

"Genetic testing is not common presently, but I do believe that there could be clinical utility for this kind of testing. The testing could be useful to target preventive interventions, such as statin medications," Kathiresan told ֱ.

Patients with the highest genetic risk may also be targeted to undergo more intensive lifestyle modification -- although whether or not that can improve hard cardiovascular outcomes remains to be seen, the BioImage investigators acknowledged.

Additionally, the authors suggested that all healthy lifestyle factors may not be equal: some may be tied to more benefit than others.

"We need to ensure that our patients understand that having both a high genetic risk and a poor lifestyle is a very dangerous combination," , of McGill University Health Centre in Montreal, told ֱ. Thanassoulis was not involved in the present study.

Kathiresan's analysis incorporated prospectively collected data from 55,685 patients from the Atherosclerosis Risk in Communities Study (n=7,814), Women's Genome Health Study (n=21,222), the Malmo Diet and Cancer Study (n=22,389), and the BioImage Study itself (n=4,260).

A healthy lifestyle was associated with a lower subclinical burden of heart disease in terms of less coronary artery calcification among all genetic risk groups (28 Agatston units for favorable lifestyle versus 28 Agatston units for unfavorable lifestyle, P<0.001).

The investigators acknowledged several limitations to their study, including its non-randomized nature and the pooling of data gathered using each cohort's different methods. In addition, the authors did not account for behavioral changes or competing illnesses that would have raised patients' risk for cardiac events

Finally, their findings have yet to be duplicated in robust ethnicity-specific data.

Thanassoulis commented: "Genetic testing for CAD is not commonly performed in a clinical context, but the evidence over the last several years is mounting that genetic testing may have clinical utility. Recent studies have shown that genetic risk can identify those individuals who are at highest risk of MI, can identify those who may benefit most from statin therapy, as well as now (with this study), those who should be encouraged, most strongly, to adhere to a healthy lifestyle."

"What we need now in the field is a randomized trial to confirm these findings in order to bring genetic testing for CAD to the clinic," he said.

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    Nicole Lou is a reporter for ֱ, where she covers cardiology news and other developments in medicine.

Disclosures

Kathiresan declared an award from Massachusetts General Hospital and support from the NIH.

BioImage was funded by a grant from the American College of Cardiology-Merck Research Fellowship, a fellowship from Harvard Medical School, an NIH-funded award from Harvard Catalyst.

Thanassoulis reported serving on the speaker bureau of Servier Canada and the advisory boards of Servier, Amgen, and Ionis; as well as consulting for Ionis.

Primary Source

The New England Journal of Medicine

Khera AV, et al "Genetic risk, adherence to a healthy lifestyle, and coronary disease" New Engl J Med 2016; DOI: 10.1056/NEJMoa1605086.